Epstein–Barr Virus–host epigenetic interplay: mechanisms of regulation and therapeutic potential

The Epstein-Barr virus (EBV) has evolved complex mechanisms to manipulate the host immune system and epigenetic machinery, enabling it to establish lifelong latent infection within host cells. Emerging evidence strongly indicates that the EBV acts as a main epigenetic manipulator by silencing host regulatory genes, altering host chromatin landscapes and exploiting B-cell biology. Key mechanisms include viral-mediated recruitment of host DNA methyltransferases and histone-modifying enzymes; modulation of host non-coding RNAs and chromatin architectural factors; and targeted disruption of interferon signaling through RNA methylation and restructuring of host chromatin. These integrated processes allow EBV to maintain a lifelong infection in humans, evade both innate and adaptive immunity, and respond to reactivation signals. Understanding the virus-host epigenetic interplay offers new opportunities for therapeutic interventions targeting epigenetic regulators in EBV-associated diseases.